THE OBJECTIVE OF THIS STUDY IS TO SYNTHESIZE, CHARACTERIZE, AND EVALUATE BIOLOGICAL PROPERTIES OF POLYMERIC PLATINUM COMPLEXES IN AN EFFORT TO ENHANCE SOLUBILITY AND STABILITY WHILE REDUCING TOXICITY AND OBTAINING GREATER SUSTAINED ACTIVITY THAN THAT

THE OBJECTIVE OF THIS STUDY IS TO SYNTHESIZE, CHARACTERIZE, AND EVALUATE BIOLOGICAL PROPERTIES OF POLYMERIC PLATINUM COMPLEXES IN AN EFFORT TO ENHANCE SOLUBILITY AND STABILITY WHILE REDUCING TOXICITY AND OBTAINING GREATER SUSTAINED ACTIVITY THAN THAT FOUND WITH ACTIVE, STRUCTURALLY RELATED, MONOMERIC COMPLEXES. THE PHASE I RESEARCH PLAN IS BASED ON THE PROMISING PRELIMINARY IN VIVO RESULTS OBTAINED FOR A DACH-PT COMPLEX WITH THE POLYANION OF POLY(METHACRYLIC ACID) (PMA), A BIOCOMPATIBLE, HYDROPHILIC POLYMER. THIS COMPLEX HAS EXHIBITED BETTER IN VIVO ANTITUMOR ACTIVITY AND THERAPEUTIC INDEX THAN THE CORRESPONDING MONOMERIC ANALOG IN TUMORED MICE. IN PHASE I RESEARCH, THE EFFECT OF MOLECULAR WEIGHT AND MICROSTRUCTURE OF PMA ON COMPLEX STABILITY AND ANTITUMOR ACTIVITY WILL BE INVESTIGATED. NEW POLYMERIC ANALOGS OF GENERAL FORMULA PT(DACH)POLYCARBOXYLATE WILL ALSO BE SYNTHESIZED AND EVALUATED IN VIVO FOR THEIR ANTITUMOR ACTIVITY AGAINST L1210 LEUKEMIA IN MICE. THE SUCCESSFUL DEVELOPMENT OF POLYMERIC PLATINUM COMPLEXES EXHIBITING ANTINEOPLASTIC ACTIVITY WILL YIELD A TOTALLY NEW CLASS OF ANTICANCER AGENTS WHOSE UNIQUE PHYSICAL AND CHEMICAL CHARACTERISTICS WOULD BE EXPECTED TO EXHIBIT SIMILARLY UNIQUE CLINICAL CHARACTERISTICS, PROSPECTIVELY ENHANCING THE THERAPEUTIC EFFECT AND ACCEPTANCE OF CHEMOTHERAPY BY CANCER PATIENTS.